10-103079395-T-C

Variant names:

• chr10-103079395-T-C
• rs943035
• NM_017649.5:c.*2215T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017649.5(CNNM2):​c.*2215T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 152,106 control chromosomes in the GnomAD database, including 12,670 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (12652 hom., cov: 31)
  • Exomes 𝑓: 0.51 (18 hom.)
• Consequence: CNNM2 NM_017649.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNNM2	NM_017649.5	c.*2215T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3
CNNM2	NM_199076.3	c.*2215T>C		3_prime_UTR_variant	Exon 7 of 7		NP_951058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9	c.*2215T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61531 AN: 151862 Hom.: 12637 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.508 AC: 65 AN: 128 Hom.: 18 Cov.: 0 AF XY: 0.488 AC XY: 42 AN XY: 86

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.405 AC: 61584 AN: 151978 Hom.: 12652 Cov.: 31 AF XY: 0.402 AC XY: 29861 AN XY: 74280

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.403

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.417

Alfa AF: 0.412 Hom.: 2121

Bravo AF: 0.408

Asia WGS AF: 0.403 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.39
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs943035; hg19: chr10-104839152;